Publications by authors named "Hui Tian"

483 Publications

Enhanced recovery after surgery improves short-term outcomes in patients undergoing esophagectomy.

Ann Thorac Surg 2021 Oct 5. Epub 2021 Oct 5.

Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, People's Republic of China. Electronic address:

Background: Enhanced recovery after surgery (ERAS) is a perioperative management protocol that aims to accelerate patient recovery. This study aimed to evaluate its benefits in patients with resectable esophageal cancer.

Methods: This retrospective study compared patients before (January 2013 to December 2016) and after (June 2018 to December 2020) ERAS protocol implementation in our hospital. A propensity score-matched (PSM) analysis was used to compare short-term surgical outcomes between ERAS and non-ERAS groups. After PSM, each group included 243 patients.

Results: There were significant differences in hospital length of stay after surgery (7.40 vs. 11.17 days, P<.001) and hospitalization cost (¥69380 vs. ¥78075, P<.001) between the ERAS and non-ERAS groups. The time to chest tube removal (4.91 vs. 7.16 days, P<.001) and first bowel movement (2.87 vs. 3.97 days, P<.001) was significantly shorter in the ERAS group. However, there was no significant difference in total postoperative complication morbidity (20.2% vs. 25.1%, P=0.193). The complication of postoperative atelectasis or pneumonia was significantly lower in the ERAS group (P=0.003), but there was no significant difference in occurrence of ≥Grade III complications between the two groups (12.3% vs. 11.5%, P=0.889).

Conclusions: We demonstrated that ERAS could reduce the hospital stay, numerical pain scores, and hospitalization costs without increasing postoperative complication and readmission. Furthermore, subgroup analyses revealed that ERAS was safe for older people (>70 years old).
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http://dx.doi.org/10.1016/j.athoracsur.2021.08.073DOI Listing
October 2021

Identification of Clinical Candidate M2698, a Dual p70S6K and Akt Inhibitor, for Treatment of PAM Pathway-Altered Cancers.

J Med Chem 2021 Oct 1;64(19):14603-14619. Epub 2021 Oct 1.

Discovery Technologies, Medicinal Chemistry, EMD Serono Research & Development Institute, Inc., Billerica, Massachusetts 01821, United States.

Herein, we report the discovery of a novel class of quinazoline carboxamides as dual p70S6k/Akt inhibitors for the treatment of tumors driven by alterations to the PI3K/Akt/mTOR (PAM) pathway. Through the screening of in-house proprietary kinase library, 4-benzylamino-quinazoline-8-carboxylic acid amide stood out, with sub-micromolar p70S6k biochemical activity, as the starting point for a structurally enabled p70S6K/Akt dual inhibitor program that led to the discovery of M2698, a dual p70S6k/Akt inhibitor. M2698 is kinase selective, possesses favorable physical, chemical, and DMPK profiles, is orally available and well tolerated, and displayed tumor control in multiple studies of PAM pathway-driven tumors.
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http://dx.doi.org/10.1021/acs.jmedchem.1c01087DOI Listing
October 2021

Identification of a Ferroptosis-Related Signature Model Including mRNAs and lncRNAs for Predicting Prognosis and Immune Activity in Hepatocellular Carcinoma.

Front Oncol 2021 9;11:738477. Epub 2021 Sep 9.

Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

Background: Ferroptosis is a novel form of regulated cell death involved in tumor progression. The role of ferroptosis-related lncRNAs in hepatocellular carcinoma (HCC) remains unclear.

Methods: RNA-seq and clinical data for HCC patients were downloaded from The Cancer Genome Atlas (TCGA) Genomic Data Commons (GDC) portal. Bioinformatics methods, including weighted gene coexpression network analysis (WGCNA), Cox regression, and least absolute shrinkage and selection operator (LASSO) analysis, were used to identify signature markers for diagnosis/prognosis. The tumor microenvironment, immune infiltration and functional enrichment were compared between the low-risk and high-risk groups. Subsequently, small molecule drugs targeting ferroptosis-related signature components were predicted the L1000FWD and PubChem databases.

Results: The prognostic model consisted of 2 ferroptosis-related mRNAs (SLC1A5 and SLC7A11) and 8 ferroptosis-related lncRNAs (AC245297.3, MYLK-AS1, NRAV, SREBF2-AS1, AL031985.3, ZFPM2-AS1, AC015908.3, MSC-AS1). The areas under the curves (AUCs) were 0.830 and 0.806 in the training and test groups, respectively. Decision curve analysis (DCA) revealed that the ferroptosis-related signature performed better than all pathological characteristics. Multivariate Cox regression analysis showed that the risk score was an independent prognostic factor. The survival probability of low- and high-risk patients could be clearly distinguished by the principal component analysis (PCA) plot. The risk score divided HCC patients into two distinct groups in terms of immune status, especially checkpoint gene expression, which was further supported by the Gene Ontology (GO) biological process, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, several small molecule drugs (SIB-1893, geldanamycin and PD-184352, etc) targeting ferroptosis-related signature components were identified for future reference.

Conclusion: We constructed a new ferroptosis-related mRNA/lncRNA signature for HCC patients. The model can be used for prognostic prediction and immune evaluation, providing a reference for immunotherapies and targeted therapies.
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http://dx.doi.org/10.3389/fonc.2021.738477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458836PMC
September 2021

Plasma Heating Induced by Tadpole-like Downflows in the Flaring Solar Corona.

Innovation (N Y) 2021 Feb 19;2(1):100083. Epub 2021 Jan 19.

Aryabhatta Research Institute of Observational Sciences, Beluwakhan, Uttarakhand 263001, India.

As one of the most spectacular energy release events in the solar system, solar flares are generally powered by magnetic reconnection in the solar corona. As a result of the re-arrangement of magnetic field topology after the reconnection process, a series of new loop-like magnetic structures are often formed and are known as flare loops. A hot diffuse region, consisting of around 5-10 MK plasma, is also observed above the loops and is called a supra-arcade fan. Often, dark, tadpole-like structures are seen to descend through the bright supra-arcade fans. It remains unclear what role these so-called supra-arcade downflows (SADs) play in heating the flaring coronal plasma. Here we show a unique flare observation, where many SADs collide with the flare loops and strongly heat the loops to a temperature of 10-20 MK. Several of these interactions generate clear signatures of quasi-periodic enhancement in the full-Sun-integrated soft X-ray emission, providing an alternative interpretation for quasi-periodic pulsations that are commonly observed during solar and stellar flares.
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http://dx.doi.org/10.1016/j.xinn.2021.100083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454670PMC
February 2021

Comparative Proteomic Analysis of Tolerant and Sensitive Varieties Reveals That Phenylpropanoid Biosynthesis Contributes to Salt Tolerance in Mulberry.

Int J Mol Sci 2021 Aug 30;22(17). Epub 2021 Aug 30.

The Sericultural and Silk Research Institute, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.

Mulberry, an important woody tree, has strong tolerance to environmental stresses, including salinity, drought, and heavy metal stress. However, the current research on mulberry resistance focuses mainly on the selection of resistant resources and the determination of physiological indicators. In order to clarify the molecular mechanism of salt tolerance in mulberry, the physiological changes and proteomic profiles were comprehensively analyzed in salt-tolerant (Jisang3) and salt-sensitive (Guisangyou12) mulberry varieties. After salt treatment, the malondialdehyde (MDA) content and proline content were significantly increased compared to control, and the MDA and proline content in G12 was significantly lower than in Jisang3 under salt stress. The calcium content was significantly reduced in the salt-sensitive mulberry varieties Guisangyou12 (G12), while sodium content was significantly increased in both mulberry varieties. Although the Jisang3 is salt-tolerant, salt stress caused more reductions of photosynthetic rate in Jisang3 than Guisangyou12. Using tandem mass tags (TMT)-based proteomics, the changes of mulberry proteome levels were analyzed in salt-tolerant and salt-sensitive mulberry varieties under salt stress. Combined with GO and KEGG databases, the differentially expressed proteins were significantly enriched in the GO terms of amino acid transport and metabolism and posttranslational modification, protein turnover up-classified in Guisangyou12 while down-classified in Jisang3. Through the comparison of proteomic level, we identified the phenylpropanoid biosynthesis may play an important role in salt tolerance of mulberry. We clarified the molecular mechanism of mulberry salt tolerance, which is of great significance for the selection of excellent candidate genes for saline-alkali soil management and mulberry stress resistance genetic engineering.
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http://dx.doi.org/10.3390/ijms22179402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431035PMC
August 2021

Pressure-Induced Variation of the Crystal Stacking Order in the Hydrogen-Bonded Quasi-Two-Dimensional Layered Material Cu(OH)Cl.

Materials (Basel) 2021 Sep 2;14(17). Epub 2021 Sep 2.

State Key Laboratory of Superhard Materials, College of Physics, Jilin University, Changchun 130012, China.

The crystal stacking order plays a crucial role in determining the structure and physical properties of 2D layered materials. A variation in the stacking sequence of adjacent 2D building blocks causes drastic changes in their functionalities. In this work, the structural variation of belloite (Cu(OH)Cl), as a function of pressure, is presented. Through in situ synchrotron X-ray diffraction and Raman scattering studies, in combination with first-principles theoretical simulations, a structural transformation from the initial monoclinic phase into an orthorhombic one has been established at 18.7 GPa, featuring variations in the stacking sequence of the tectonic monolayers. In the monoclinic phase, they are arranged in an AAAA sequence. While in the orthorhombic phase, the monolayers are stacked in an ABAB sequence. Such phenomena are similar to those observed in van der Waals 2D materials, with pressure-induced changes in the stacking order between layers. In addition, an isostructural phase transition within the initial monoclinic phase is also observed to occur at 12.9-16 GPa, which is associated with layer-sliding and a change in hydrogen bond configuration. These results show that Cu(OH)Cl, as well as other hydrogen-bonded 2D layered materials, can provide a convenient platform for studying the effects of the crystal stacking order.
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http://dx.doi.org/10.3390/ma14175019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434516PMC
September 2021

Exosomal ERp44 derived from ER-stressed cells strengthens cisplatin resistance of nasopharyngeal carcinoma.

BMC Cancer 2021 Sep 8;21(1):1003. Epub 2021 Sep 8.

Department of Otorhinolaryngology Head and Neck surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.

Background: Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in head and neck. Platinum-based chemotherapy is an important treatment for NPC. However, the molecular mechanism of resistance to platinum drug remains unknown. Endoplasmic reticulum resident protein 44(ERp44), an unfolded protein response (UPR)-induced endoplasmic reticulum(ER) protein, is induced during ER stress. This research explored the mechanism of ERp44 in strengthening cisplatin resistance in NPC.

Methods: Western blot and immunohistochemistry were used to investigate the expression of ERp44 and Glucose-Regulated Protein 78(GRP78) in NPC. We took CCK8 to detect the role of ERp44 on cell chemosensitivity. Flow cytometric analysis and western blot were taken to analyze cell apoptosis. We performed differential centrifugation to isolate exosomes from serum or conditioned media of cells and analyzed the impact of exosomal ERp44 on cells cisplatin sensitivity. Finally, the results were confirmed in vivo.

Results: We found the increased expression of ERp44 and GRP78 in NPC and ERp44 was highly expressed in ER-stressed tissues. Cell proliferation was inhibited after cisplatin treatment when ERp44 was knocked down and ERp44 strengthened cisplatin resistance by influencing cell apoptosis and pyroptosis. Then we also collected exosomes and cell viability was increased after the addition of NPC-derived-exosomes with cisplatin treatment. More importantly, our results showed under ERS, NPC cells secreted exosomes containing ERp44 and could transfer them to adjacent cells to strengthen chemoresistance.

Conclusion: Our data suggested that exosomal ERp44 derived from ER-stressed NPC cells took an inevitable role in NPC chemoresistance and might act as a treatment target.
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http://dx.doi.org/10.1186/s12885-021-08712-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424889PMC
September 2021

Discovery of 4-aminopyrimidine analogs as highly potent dual P70S6K/Akt inhibitors.

Bioorg Med Chem Lett 2021 Oct 2;50:128352. Epub 2021 Sep 2.

EMD Serono Research and Development Institute, Inc., 45A Middlesex Turnpike, Billerica, MA 01821, USA.

Activation of the PI3K/Akt/mTOR kinase pathway is associated with human cancers. A dual p70S6K/Akt inhibitor is sufficient to inhibit strong tumor growth and to block negative impact of the compensatory Akt feedback loop activation. A scaffold docking strategy based on an existing quinazoline carboxamide series identified 4-aminopyrimidine analog 6, which showed a single-digit nanomolar and a micromolar potencies in p70S6K and Akt enzymatic assays. SAR optimization improved Akt enzymatic and p70S6K cellular potencies, reduced hERG liability, and ultimately discovered the promising candidate 37, which exhibited with a single digit nanomolar value in both p70S6K and Akt biochemical assays, and hERG activities (IC = 17.4 μM). This agent demonstrated dose-dependent efficacy in inhibiting mice breast cancer tumor growth and covered more than 90% pS6 inhibition up to 24 h at a dose of 200 mg/kg po.
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http://dx.doi.org/10.1016/j.bmcl.2021.128352DOI Listing
October 2021

Polyaspartic acid alleviates cadmium toxicity in rapeseed leaves by affecting cadmium translocation and cell wall fixation of cadmium.

Ecotoxicol Environ Saf 2021 Aug 20;224:112685. Epub 2021 Aug 20.

College of Resources and Environmental Sciences, Hunan Agricultural University, Changsha, China. Electronic address:

Polyaspartic acid (PASP) is a macromolecule compound with carboxylic acid side chains which is polymerized by L-aspartic acid, has been used as a biodegradable and environmentally-friendly chelating agent to enhance the phytoremediation of heavy metal-contaminated soils. Cadmium (Cd) is a toxic element for plant growth, productivity, and food security. To reveal the responses of PASP to plant physiology and morphology under Cd stress, we comprehensively analyzed soil characteristics, cell ultrastructure, reactive oxygen species (ROS), antioxidant enzymes, Cd uptake, transport, subcellular distribution, cell wall compositions, and their Cd chelating capacity in rapeseed. The results showed PASP increased the content of total N, total P, and available P in soil by 3.4%, 28.6%, and 39.8%, respectively, but did not change soil pH and available Cd. Meanwhile, PASP promoted dry mass accumulation and increased photosynthetic pigment content in rapeseed leaves by maintaining the chloroplast structure. Lower malondialdehyde (MDA) content and hydrogen peroxide (HO) accumulation and activated antioxidant enzymes in leaves indicate that PASP contributed to relieving Cd-induced oxidative damage to cells of rapeseed leaves. The results indicated that PASP application increased the Cd distribution ratio in root cell walls from 47.4% to 62.3% and decreased the Cd content in xylem sap by 37.8%, which ultimately reduced Cd reallocation in leaves. Additionally, higher pectin content and Cd in pectin resulted in higher Cd retention in leaf cell walls while reducing its concentration in the organelle fraction. The results indicated that 0.3% PASP effectively alleviated Cd stress in rapeseed leaves by inhibiting Cd transportation from roots, activating antioxidant enzymes to scavenge ROS, and promoting Cd chelation by cell wall pectin in leaves.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112685DOI Listing
August 2021

Circadian Clock Genes REV-ERBs Inhibits Granulosa Cells Apoptosis by Regulating Mitochondrial Biogenesis and Autophagy in Polycystic Ovary Syndrome.

Front Cell Dev Biol 2021 5;9:658112. Epub 2021 Aug 5.

Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.

Polycystic ovary syndrome (PCOS) is an endocrinopathy with complex pathophysiology that is a common cause of anovulatory infertility in women. Although the disruption of circadian rhythms is indicated in PCOS, the role of the clock in the etiology of these pathologies has yet to be appreciated. The nuclear receptors REV-ERBα and REV-ERBβ are core modulators of the circadian clock and participate in the regulation of a diverse set of biological functions. However, in PCOS, the expression of REV-ERBs and their effects remain unclear. Here, we demonstrate that the levels of REV-ERBα and REV-ERBβ expression were lower in the granulosa cells of PCOS patients than in control subjects. , we found that the overexpression of REV-ERBα and REV-ERBβ, and their agonist SR9009, promoted the expression of mitochondrial biosynthesis genes PGC-1α, NRF1, and TFAM and inhibited autophagy in KGN cells. Our results also indicate that REV-ERBα and REV-ERBβ can inhibit apoptosis in granulosa cells and promote proliferation. Importantly, the REV-ERB agonist SR9009 ameliorates abnormal follicular development by promoting mitochondrial biosynthesis and inhibiting autophagy in a mouse PCOS model. This allows us to speculate that SR9009 has potential as a therapeutic agent for the treatment of PCOS.
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http://dx.doi.org/10.3389/fcell.2021.658112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374745PMC
August 2021

Phase 1 study of M2698, a p70S6K/AKT dual inhibitor, in patients with advanced cancer.

J Hematol Oncol 2021 08 18;14(1):127. Epub 2021 Aug 18.

Moores Cancer Center, La Jolla, CA, USA.

Background: The PI3K/AKT/mTOR (PAM) pathway is a key regulator of tumor therapy resistance. We investigated M2698, an oral p70S6K/AKT dual inhibitor, in patients with advanced cancer who failed standard therapies.

Methods: M2698 was administered as monotherapy (escalation, 15-380 mg daily; food effect cohort, 240-320 mg daily) and combined with trastuzumab or tamoxifen.

Results: Overall, 101 patients were treated (M2698, n = 62; M2698/trastuzumab, n = 13; M2698/tamoxifen, n = 26). Patients were predominantly aged < 65 years, were female, had performance status 1 and were heavily pretreated. There was a dose- and concentration-dependent inhibition of pS6 levels in peripheral blood mononuclear cells and tumor tissue. M2698 was well tolerated; the most common treatment-emergent adverse events were gastrointestinal, abnormal dreams and fatigue (serious, attributed to M2698: monotherapy, 8.1%; M2698/trastuzumab, 7.7%; M2698/tamoxifen, 11.5% of patients). The recommended phase 2 doses of M2698 were 240 mg QD (monotherapy), 160 mg QD (M2698/trastuzumab) and 160 mg QD/240 mg intermittent regimen (M2698/tamoxifen). In the monotherapy cohort, 27.4% of patients had stable disease at 12 weeks; no objective response was noted. The median progression-free survival (PFS) durations in patients with PAM pathway alterations with and without confounding markers (KRAS, EGFR, AKT2) were 1.4 months and 2.8 months, respectively. Two patients with breast cancer (M2698/trastuzumab, n = 1; M2698/tamoxifen, n = 1) had partial response; their PFS durations were 31 months and 2.7 months, respectively.

Conclusions: M2698 was well tolerated. Combined with trastuzumab or tamoxifen, M2698 demonstrated antitumor activity in patients with advanced breast cancer resistant to multiple standard therapies, suggesting that it could overcome treatment resistance. Trial registration ClinicalTrials.gov, NCT01971515. Registered October 23, 2013.
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http://dx.doi.org/10.1186/s13045-021-01132-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371902PMC
August 2021

Integrated bioinformatics analysis of differentially expressed genes and immune cell infiltration characteristics in Esophageal Squamous cell carcinoma.

Sci Rep 2021 08 17;11(1):16696. Epub 2021 Aug 17.

Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.

Esophageal squamous cell carcinoma (ESCC) is a life-threatening thoracic tumor with a poor prognosis. The role of molecular alterations and the immune microenvironment in ESCC development has not been fully elucidated. The present study aimed to elucidate key candidate genes and immune cell infiltration characteristics in ESCC by integrated bioinformatics analysis. Nine gene expression datasets from the Gene Expression Omnibus (GEO) database were analysed to identify robust differentially expressed genes (DEGs) using the robust rank aggregation (RRA) algorithm. Functional enrichment analyses showed that the 152 robust DEGs are involved in multiple processes in the tumor microenvironment (TME). Immune cell infiltration analysis based on the 9 normalized GEO microarray datasets was conducted with the CIBERSORT algorithm. The changes in macrophages between ESCC and normal tissues were particularly obvious. In ESCC tissues, M0 and M1 macrophages were increased dramatically, while M2 macrophages were decreased. A robust DEG-based protein-protein interaction (PPI) network was used for hub gene selection with the CytoHubba plugin in Cytoscape. Nine hub genes (CDA, CXCL1, IGFBP3, MMP3, MMP11, PLAU, SERPINE1, SPP1 and VCAN) had high diagnostic efficiency for ESCC according to receiver operating characteristic (ROC) curve analysis. The expression of all hub genes except MMP3 and PLAU was significantly related to macrophage infiltration. Univariate and multivariate regression analyses showed that a 7-gene signature constructed from the robust DEGs was useful for predicting ESCC prognosis. Our results might facilitate the exploration of potential targeted TME therapies and prognostic evaluation in ESCC.
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http://dx.doi.org/10.1038/s41598-021-96274-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371051PMC
August 2021

Effects of UCMSCs Delivered through Different Transplantation Approaches on Acute Radiation Enteritis in Rats.

Cell Transplant 2021 Jan-Dec;30:9636897211025230

Medical School of Kunming University, Kunming, China.

Radiation enteritis is the most common and serious complication of abdominal or pelvic radiation therapy. Mesenchymal stem cells (MSCs), as well as cell protection agents, inhibit apoptosis and promote the proliferation of injured tissues. 3 human umbilical cords MSCs (UCMSCs) were injected into the tail vein or peritoneal cavity of a rat model of radiation enteritis. The temporary protective effect was assessed by identification of donor cells, detection of cellular immune parameters and inflammatory cytokine levels, quantitation of jejunum mucosal preservation and examination of the rat remaining life. Only the rats in the intraperitoneal injection group exhibited a few positive donor cells 7 days after transplantation. CD /CD T cells, a cellular immune parameter, decreased in the abdominal exudate of intraperitoneal injection group, compared with the model-only control and tail vein groups (both < .05). Both serum and abdominal exudate TNF-α and IL-6 levels in the intraperitoneally injected rats rapidly decreased and were significantly different from those in the model-only control and tail vein injection groups (all < .05). Mucosal surface area and survival time increased in the intraperitoneal injection group compared with the vehicle and tail vein injection groups (all = .000). Therefore, the administration of UCMSCs with intraperitoneal injection approach postponed death in a rat model of radiation enteritis, which was associated with reduced serum levels of proinflammatory cytokines (TNF-α, IL-6). However, UCMSCs injected via the tail vein triggered an intense cellular immune response in the serum that adversely affects their survival. This treatment failed to suppress circulating serum and abdominal exudate levels of TNF-α and IL-6 and could not provide a therapeutic benefit for prolonging life against acute radiation enteritis.
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http://dx.doi.org/10.1177/09636897211025230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323445PMC
July 2021

The effect of the enhanced recovery after surgery program on lung cancer surgery: a systematic review and meta-analysis.

J Thorac Dis 2021 Jun;13(6):3566-3586

Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Lung cancer is one of the most common causes of cancer-related death worldwide. The enhanced recovery after surgery (ERAS) program is an effective evidence-based multidisciplinary protocol of perioperative care. However, the roles of ERAS in lung cancer surgery remain unclear. This systematic review and meta-analysis aimed to investigate the short-term impact of the ERAS program on lung resection surgery, especially in relation to postoperative complications.

Methods: A systematic literature search of PubMed, EMBASE, and the Cochrane Library databases until October 2020 was performed to identify the studies that implemented an ERAS program in lung cancer surgery. The studies were selected and subjected to data extraction by 2 reviewers independently, which was followed by quality assessment. A random effects model was used to calculate overall effect sizes. Risk ratio (RR), risk difference (RD), and standardized mean difference (SMD) with 95% confidence interval (CI) served as the summary statistics for meta-analysis. Subgroup analysis and sensitivity analysis were subsequently performed.

Results: A total of 21 studies with 6,480 patients were included. The meta-analysis indicated that patients in the ERAS group had a significantly reduced risk of postoperative complications (RR =0.64; 95% CI: 0.52 to 0.78) and shortened postoperative length of stay (SMD=-1.58; 95% CI: -2.38 to -0.79) with a significant heterogeneity. Subgroup analysis showed that the risks of pulmonary (RR =0.58; 95% CI: 0.45 to 0.75), cardiovascular (RR =0.73; 95% CI: 0.59 to 0.89), urinary (RR =0.53; 95% CI: 0.32 to 0.88), and surgical complications (RR =0.64; 95% CI: 0.42 to 0.97) were significantly lower in the ERAS group. No significant reduction was found in the in-hospital mortality (RD =0.00; 95% CI: -0.01 to 0.00) and readmission rate (RR =1.00; 95% CI: 0.76 to 1.32). In the qualitative review, most of the evidence reported significantly decreased hospitalization costs in the ERAS group.

Conclusions: The implementation of an ERAS program for surgery of lung cancer can effectively reduce risks of postoperative complications, length of stay, and costs of patients who have undergone lung cancer surgery without compromising their safety.
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http://dx.doi.org/10.21037/jtd-21-433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264698PMC
June 2021

Circ-PRKCI Alleviates Lipopolysaccharide-induced Human Kidney 2 Cell Injury by Regulating miR-106b-5p/GAB1 Axis.

J Cardiovasc Pharmacol 2021 Oct;78(4):523-533

Department of Infectious Diseases, Huaihe Hospital of Henan University, Kaifeng, Henan, China; and.

Abstract: Circular RNAs act as vital regulators in diverse diseases. However, the investigation of circular RNAs in sepsis-engendered acute kidney injury remains dismal. We aimed to explore the effects of circular RNA protein kinase C iota (circ-PRKCI) in lipopolysaccharide (LPS)-mediated HK2 cell injury. Sepsis in vitro model was established by LPS treatment. Quantitative real-time polymerase chain reaction assay was conducted for determining the levels of circ-PRKCI, microRNA-106b-5p (miR-106b-5p), and growth factor receptor binding 2-associated binding protein 1 (GAB1). Cell viability and apoptosis were evaluated using Cell Counting Kit-8 assay and flow cytometry analysis, respectively. The concentrations of interleukin-6, interleukin-1β, and tumor necrosis factor-α were measured with enzyme-linked immunosorbent assay kits. The levels of oxidative stress markers were determined using relevant commercial kits. Western blot assay was conducted for B-cell lymphoma-2 (Bcl-2), BCL2-Associated X (Bax), and GAB1 protein levels. Dual-luciferase reporter assay and RNA immunoprecipitation assay were used to verify the association between miR-106b-5p and circ-PRKCI or GAB1. We found the Circ-PRKCI level was decreased in sepsis patients and LPS-induced human kidney 2 (HK-2) cells. LPS exposure inhibited cell viability and facilitated apoptosis, inflammation, and oxidative stress in HK-2 cells. Circ-PRKCI overexpression abrogated the effects of LPS on cell apoptosis, inflammation, and oxidative stress in HK-2 cells. Furthermore, circ-PRKCI was identified as the sponge for miR-106b-5p to positively regulate GAB1 expression. Overexpression of circ-PRKCI relieved LPS-mediated HK-2 cell damage by sponging miR-106b-5p. MiR-106b-5p inhibition ameliorated the injury of HK-2 cells mediated by LPS, whereas GAB1 knockdown reversed the effect. Collectively, Circ-PRKCI overexpression attenuated LPS-induced HK-2 cell injury by regulating miR-106b-5p/GAB1 axis.
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http://dx.doi.org/10.1097/FJC.0000000000001031DOI Listing
October 2021

Pressure-Induced Electronic and Structural Transition in Nodal-Line Semimetal ZrSiSe.

Inorg Chem 2021 Aug 9;60(15):11140-11146. Epub 2021 Jul 9.

State Key Laboratory of Superhard Materials, Jilin University, Changchun 130012, China.

The nodal-line semimetals have recently gained attention as a promising material due to their exotic electronic structure and properties. Here, we investigated the structural evolution and physical properties of nodal-line semimetal ZrSiSe under pressure via experiments and theoretical calculations. An isostructural electronic transition is observed at ∼6 GPa. Upon further compression, the original tetragonal phase starts to transform into an orthorhombic phase at ∼13 GPa and the two phases coexist until the maximal experimental pressure. By analysis of the electronic band structure, we suggest that the significant changes in the Fermi surface contribute to the occurrence of the isostructural electronic transition. The results provide a new insight into the structure and properties of ZrSiSe.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01087DOI Listing
August 2021

The Role of Color Doppler Ultrasonography in the Perioperative Period of Coronary Artery Bypass Grafting: Comparison with Transit-Time Flow Measurement.

Cardiology 2021 30;146(5):583-590. Epub 2021 Jun 30.

Department of Ultrasound, Peking University People's Hospital, Beijing, China.

Introduction: The value of color Doppler ultrasonography (CDUS) with the supraclavicular approach for preoperative evaluation of the native left internal mammary artery (LIMA) as well as for the postoperative detection of LIMA graft patency was recently suggested. However, the parameters such as the flow volume and pulsatile index (PI) have not been studied in detail.

Objectives: The objectives of this study were to analyze the LIMA data in the perioperative period and explore the relationships between the intraoperative graft flow with transit-time flow measurement (TTFM) and the postoperatively measured parameters with CDUS.

Methods: Fifty-eight patients with significant stenosis (≥70%) or occlusions in left anterior descending artery (LAD) who were referred for isolated coronary artery bypass grafting (CABG) were enrolled in this study and examined by CDUS prior to CABG from April to July 2016. The perioperative measurements of proximal LIMA by CDUS were compared. In addition, the correlation between the intraoperative graft flow, such as the mean graft flow (MGF) and PI, and the immediate postoperative measurements of CDUS in LIMA bypassed grafts was statistically analyzed.

Results: Six patients were excluded due to screening failure, or insufficient visualization of CDUS images for analysis. Fifty-two patients with in situ LIMA-LAD graft, with or without additional arterial grafts or saphenous vein grafts, were included in the final analysis. The postoperative diameters of proximal LIMA were not significantly different from preoperative diameters (2.21 ± 0.18 vs. 2.27 ± 0.22 mm, p = 0.070). The flow volume on the early postoperative CDUS significantly increased (39.77 ± 21.59 vs. 25.96 ± 13.17 mL/min, p < 0.001) and the PI significantly decreased (1.43 ± 0.46 vs. 4.20 ± 1.49, p < 0.001) versus those of preoperative measurements. The MGF had a moderate correlation with the flow volume on the early postoperative CDUS (r = 0.414, p = 0.002), and the PI by TTFM had a weak correlation with that by CDUS (r = 0.353, p = 0.010) as well.

Conclusions: The MGF and PI by TTFM in CABG were associated with in situ LIMA graft parameters measured by CDUS studies. CDUS is a useful functional noninvasive tool for the preoperative screening and postoperative follow-up of patients with in situ LIMA bypass.
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http://dx.doi.org/10.1159/000512430DOI Listing
June 2021

Co-immunization with L-Myc enhances CD8 or CD103 DCs mediated tumor-specific multi-functional CD8 T cell responses.

Cancer Sci 2021 Sep 10;112(9):3469-3483. Epub 2021 Jul 10.

Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, China.

Renal carcinoma shows a high risk of invasion and metastasis without effective treatment. Herein, we developed a chitosan (CS) nanoparticle-mediated DNA vaccine containing an activated factor L-Myc and a tumor-specific antigen CAIX for renal carcinoma treatment. The subcutaneous tumor models were intramuscularly immunized with CS-pL-Myc/pCAIX or control vaccine, respectively. Compared with single immunization group, the tumor growth was significantly suppressed in CS-pL-Myc/pCAIX co-immunization group. The increased proportion and mature of CD11c DCs, CD8 CD11c DCs and CD103 CD11c DCs were observed in the splenocytes from CS-pL-Myc/pCAIX co-immunized mice. Furthermore, the enhanced antigen-specific CD8 T lymphocyte proliferation, cytotoxic T lymphocyte (CTL) responses, and multi-functional CD8 T cell induction were detected in CS-pL-Myc/pCAIX co-immunization group compared with CS-pCAIX immunization group. Of note, the depletion of CD8 T cells resulted in the reduction of CD8 T cells or CD8 CD11c DCs and the loss of anti-tumor efficacy induced by CS-pL-Myc/pCAIX vaccine, suggesting the therapeutic efficacy of the vaccine was required for CD8 DCs and CD103 DCs mediated CD8 T cells responses. Likewise, CS-pL-Myc/pCAIX co-immunization also significantly inhibited the lung metastasis of renal carcinoma models accompanied with the increased induction of multi-functional CD8 T cell responses. Therefore, these results indicated that CS-pL-Myc/pCAIX vaccine could effectively induce CD8 DCs and CD103 DCs mediated tumor-specific multi-functional CD8 T cell responses and exert the anti-tumor efficacy. This vaccine strategy offers a potential and promising approach for solid or metastatic tumor treatment.
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http://dx.doi.org/10.1111/cas.15044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409417PMC
September 2021

LncRNA DPP10-AS1 promotes malignant processes through epigenetically activating its cognate gene DPP10 and predicts poor prognosis in lung cancer patients.

Cancer Biol Med 2021 Jun 9. Epub 2021 Jun 9.

Department of Biochemistry and Molecular Biology, Ningbo University School of Medicine, Ningbo 315211, China.

Objective: The purpose of this study was to explore the function and gene expression regulation of the newly identified lncRNA DPP10-AS1 in lung cancer, and its potential value as a prognostic biomarker.

Methods: qRT-PCR and Western blot were conducted to detect the expression of DDP10-AS1 and DPP10 in lung cancer cell lines and tissues. The effects of DDP10-AS1 on DPP10 expression, cell growth, invasion, apoptosis, and tumor growth were investigated in lung cancer cells by Western blot, rescue experiments, colony formation, flow cytometry, and xenograft animal experiments.

Results: The novel antisense lncRNA DPP10-AS1 was found to be highly expressed in cancer tissues ( < 0.0001), and its upregulation predicted poor prognosis in patients with lung cancer ( = 0.0025). Notably, DPP10-AS1 promoted lung cancer cell growth, colony formation, and cell cycle progression, and repressed apoptosis in lung cancer cells by upregulating DPP10 expression. Additionally, DPP10-AS1 facilitated lung tumor growth upregulation of DPP10 protein in a xenograft mouse model. Importantly, DPP10-AS1 positively regulated gene expression, and both were coordinately upregulated in lung cancer tissues. Mechanically, DPP10-AS1 was found to associate with mRNA but did not enhance mRNA stability. Hypomethylation of DPP10-AS1 and contributed to their coordinate upregulation in lung cancer.

Conclusions: These findings indicated that the upregulation of the antisense lncRNA DPP10-AS1 promotes lung cancer malignant processes and facilitates tumorigenesis by epigenetically regulating its cognate sense gene . DPP10-AS1 may serve as a candidate prognostic biomarker and a potential therapeutic target in lung cancer.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330531PMC
June 2021

Mouse EWSR1 is crucial for spermatid post-meiotic transcription and spermiogenesis.

Development 2021 06 8;148(11). Epub 2021 Jun 8.

The Jackson Laboratory, Bar Harbor, ME 04609, USA.

Spermatogenesis is precisely controlled by complex gene-expression programs. During mammalian male germ-cell development, a crucial feature is the repression of transcription before spermatid elongation. Previously, we discovered that the RNA-binding protein EWSR1 plays an important role in meiotic recombination in mouse, and showed that EWSR1 is highly expressed in late meiotic cells and post-meiotic cells. Here, we used an Ewsr1 pachytene stage-specific knockout mouse model to study the roles of Ewsr1 in late meiotic prophase I and in spermatozoa maturation. We show that loss of EWSR1 in late meiotic prophase I does not affect proper meiosis completion, but does result in defective spermatid elongation and chromocenter formation in the developing germ cells. As a result, male mice lacking EWSR1 after pachynema are sterile. We found that, in Ewsr1 CKO round spermatids, transition from a meiotic gene-expression program to a post-meiotic and spermatid gene expression program related to DNA condensation is impaired, suggesting that EWSR1 plays an important role in regulation of spermiogenesis-related mRNA synthesis necessary for spermatid differentiation into mature sperm.
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http://dx.doi.org/10.1242/dev.199414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217706PMC
June 2021

MCTS1 promotes the development of lung adenocarcinoma by regulating E2F1 expression.

Oncol Lett 2021 Jul 17;22(1):531. Epub 2021 May 17.

Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer that results in the majority of cancer-associated mortality. Multiple copies in T-cell lymphoma-1 (MCTS1) is an oncogene that is expressed at high levels in several types of cancer tissues. However, its exact role and pathomechanism in the development of LUAD remains unknown. Reverse transcription-quantitative PCR analysis was performed to detect MCTS1 expression. Immunohistochemistry analysis was performed to detect MCTS1 expression in LUAD tissues and normal tissues. The MTT, colony formation, EdU, flow cytometry, wound healing and Transwell assays were performed to assess the proliferation, apoptosis, migration and invasion of LUAD cells. Western blot analysis was performed to detect protein expression levels. The present study aimed to investigate the effects of MCTS1 on the progression of LUAD and the potential mechanisms underlying its effects. The results demonstrated that MCTS1 expression was upregulated in LUAD tissues and cells, which was associated with an unfavorable outcome in patients with LUAD. MCTS1 knockdown inhibited LUAD progression by suppressing cell viability and motility, and promoting apoptosis. In addition, E2F1 protein expression was attenuated following MCTS1 knockdown. The silencing MCTS1-induced inhibitory effect on LUAD malignancy was reversed following overexpression of E2F1 by modulating the c-Myc signaling pathway. Taken together, the results of the present study suggest that MCTS1 facilitates cell proliferation and migration, and suppresses apoptosis of LUAD cells by regulating E2F1 expression and the c-Myc signaling pathway.
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http://dx.doi.org/10.3892/ol.2021.12792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156638PMC
July 2021

Let-7b-3p inhibits tumor growth and metastasis by targeting the BRF2-mediated MAPK/ERK pathway in human lung adenocarcinoma.

Transl Lung Cancer Res 2021 Apr;10(4):1841-1856

Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Lung cancer is a malignant tumor with the highest morbidity and mortality rates worldwide, of which lung adenocarcinoma (LUAD) is the most common subtype. Overall, current treatments of LUAD are not satisfactory; therefore, novel targets need to be explored. Let-7b-3p is an important member of the let-7 family of microRNAs (miRNAs), and has not been studied separately in LUAD. This study aimed to investigate the role and molecular mechanism of let-7b-3p in LUAD.

Methods: Herein, let-7b-3p expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence hybridization (FISH) assays. MTT, colony formation assay, flow cytometry analysis, wound-healing, Transwell and experiments were conducted to assess let-7b-3p's function in LUAD. The downstream target TFIIB-related factor 2 (BRF2) was predicted using bioinformatics analyses and confirmed by dual-luciferase reporter assay and rescue experiments. Additionally, BRF2 was found to affect the MAPK/ERK pathway through transcriptome sequencing analysis and western blot (WB) assay.

Results: Let-7b-3p is downregulated in LUAD cells and tissue samples and low let-7b-3p expression is correlated with a poor prognosis in LUAD patients. Let-7b-3p suppresses the proliferation and metastasis of LUAD cells both and by directly targeting the BRF2-mediated MAPK/ERK pathway.

Conclusions: Let-7b-3p inhibits the development of LUAD and is an ideal novel therapeutic target for the treatment of LUAD.
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http://dx.doi.org/10.21037/tlcr-21-299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107730PMC
April 2021

Chimeric Phi29 DNA polymerase with helix-hairpin-helix motifs shows enhanced salt tolerance and replication performance.

Microb Biotechnol 2021 07 19;14(4):1642-1656. Epub 2021 May 19.

Research Center of Molecular Diagnostics and Sequencing, Research Institute of Tsinghua University in Shenzhen, Shenzhen, Guangdong, 518057, China.

Phi29 DNA polymerase (Phi29 Pol) has been successfully applied in DNA nanoball-based sequencing, real-time DNA sequencing from single polymerase molecules and nanopore sequencing employing the sequencing by synthesis (SBS) method. Among these, polymerase-assisted nanopore sequencing technology analyses nucleotide sequences as a function of changes in electrical current. This ionic, current-based sequencing technology requires polymerases to perform replication at high salt concentrations, for example 0.3 M KCl. Nonetheless, the salt tolerance of wild-type Phi29 Pol is relatively low. Here, we fused helix-hairpin-helix (HhH) domains E-L (eight repeats in total) of topoisomerase V (Topo V) from the hyperthermophile Methanopyrus kandleri to the Phi29 Pol COOH terminus, designated Phi29EL DNA polymerase (Phi29EL Pol). Domain fusion increased the overall enzyme replication efficiency by fourfold. Phi29EL Pol catalysed rolling circle replication in a broader range of salt concentrations than did Phi29 Pol, extending the KCl concentration range for activity up to 0.3 M. In addition, the mutation of Glu to Ser or Gln increased Phi29EL Pol activity in the presence of KCl. In this work, we produced a salt-tolerant Phi29 Pol derivative by means of (HhH) domain insertion. The multiple advantages of this insertion make it a good substitute for Phi29 Pol, especially for use in nanopore sequencing or other circumstances that require high salt concentrations.
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http://dx.doi.org/10.1111/1751-7915.13830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313265PMC
July 2021

Genetic transformation system for Bacillus velezensis NSZ-YBGJ001 and curing of the endogenous plasmid pBV01.

Biotechnol Lett 2021 Aug 18;43(8):1595-1605. Epub 2021 May 18.

Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, No. 12 Zhongguancun South Street, Beijing, 100081, China.

Objectives: To construct a genetic transformation system for Bacillus velezensis NSZ-YBGJ001 and identify the origin element in an endogenous plasmidpBV01 for curing pBV01 by plasmid incompatibility.

Results: A plasmid pUBC01 was constructed, and then an electrotransformation system for B. velezensis NSZ-YBGJ001 was developed, which reached ~ 1000 transformants per microgram of pUBC01 DNA. Additionally, a 7276-bp circular plasmid pBV01 with a G + C content of 37.5% was isolated from B. velezensis NSZ-YBGJ001 and analyzed via sequence analysis. To cure pBV01, an incompatible plasmid pBV02 harboring the replication element of pBV01 was developed and functionally replicated in both Bacillus subtilis WB600 and B. velezensis NSZ-YBGJ001. pBV01 was cured through introduction of pBV02 into B. velezensis NSZ-YBGJ001 after serial subculturing for approximately 40 generations. Finally, another plasmid, pBV03, was constructed based on pBV-ori, and exogenous genes in pBV03 could be efficiently expressed in B. subtilis.

Conclusions: The results of this study, including the genetic transformation system, plasmid-curing strategy, and exogenous gene expression, will support genetic manipulation of B. velezensis to promote its application in biocontrol and industry.
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http://dx.doi.org/10.1007/s10529-021-03127-9DOI Listing
August 2021

Higher Cd-accumulating oilseed rape has stronger Cd tolerance due to stronger Cd fixation in pectin and hemicellulose and higher Cd chelation.

Environ Pollut 2021 Sep 24;285:117218. Epub 2021 Apr 24.

Southern Regional Collaborative Innovation Center for Grain and Oil Crops in China, College of Resources and Environmental Sciences, Hunan Agricultural University, Changsha, China. Electronic address:

Oilseed rape (Brassica napus) has potential as a hyperaccumulator in the phytoremediation of cadmium (Cd)-contaminated soils. Oilseed rape varieties with higher Cd accumulation ability and Cd tolerance are ideal candidates for the hyperaccumulation of excess Cd. To explore the physiological and molecular mechanisms underlying Cd tolerance and high Cd accumulation in oilseed rape leaves, we examined two genotypes, "BN067" (Cd-sensitive with lower Cd accumulation in leaves) and "BN06" (Cd-tolerant with higher Cd accumulation in leaves). We characterized the physiological morphology, structure, subcellular distribution of Cd, cell wall components, cell chelates, and the transcriptional levels of the related genes. Greater Cd accumulation was observed in the cell walls and vacuoles of Cd-tolerant leaves, reducing Cd toxicity to the lamellar structure of the chloroplast thylakoid and leaf stomata. Higher expression of PMEs genes and lower expression of pectin methylesterase inhibitors (PMEI) genes improved pectin methylesterase (PME) activity in leaves of Cd-tolerant genotype. Stronger demethylation of pectin along with higher pectin and hemicellulose levels induced by lower pectinase and hemicellulose activities in the leaves of the Cd-tolerant genotype, resulting in higher Cd retention in the cell walls. Under Cd toxicity, higher Cd sequestration within the vacuoles of Cd-tolerant leaves was closely related to greater accumulation of Cd chelates with stronger biosynthesis in protoplasts. The results highlight the importance of using hyperaccumulation by plants to remediate our environment, and also provide a theoretical basis for the development of Cd-tolerant varieties.
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http://dx.doi.org/10.1016/j.envpol.2021.117218DOI Listing
September 2021

Identification and Expression Analysis of / Gene Family in L.

Int J Mol Sci 2021 Apr 28;22(9). Epub 2021 Apr 28.

College of Natural Resource and Environment, Northwest A&F University, Yangling 712100, China.

Slow type anion channels (SLAC/SLAHs) play important roles during anion transport, growth and development, abiotic stress responses and hormone responses in plants. However, there is few report on SLAC/SLAHs in rapeseed (). Genome-wide identification and expression analysis of / gene family members were performed in . A total of 23 / genes were identified in . Based on the structural characteristics and phylogenetic analysis of these members, the SLAC/SLAHs could be classified into three main groups. Transcriptome data demonstrated that genes were detected in various tissues of the rapeseed and could be up-regulated by low nitrate treatment in roots. BnSLAC/SLAHs were exclusively localized on the plasma membrane in transient expression of tobacco leaves. These results will increase our understanding of the evolution and expression of the SLAC/SLAHs and provide evidence for further research of biological functions of candidates in .
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http://dx.doi.org/10.3390/ijms22094671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125795PMC
April 2021

[Expert Consensus for Thermal Ablation of Pulmonary Subsolid Nodules (2021 Edition)].

Zhongguo Fei Ai Za Zhi 2021 May 26;24(5):305-322. Epub 2021 Apr 26.

Department of Oncology, Tengzhou Central People's Hospital, Tengzhou 277500, China.

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2021.101.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174112PMC
May 2021

G protein gamma 7 suppresses progression of lung adenocarcinoma by inhibiting E2F transcription factor 1.

Int J Biol Macromol 2021 Jul 14;182:858-865. Epub 2021 Apr 14.

Department of radiation oncology, QiLu hospital of ShanDong university, Jinan, Shandong 250012, PR China. Electronic address:

G protein gamma 7 (GNG7) has been found to be aberrantly expressed in some kinds of malignant tumors. In this study, we mainly discuss the antitumor role of it in lung adenocarcinoma (LUAD) cells. Protein levels of GNG7 in LUAD tissues were measured by western blot and immunohistochemical analysis. Cell proliferation, invasion and migration were detected by CCK-8 assay, 5-ethynyl-2'-deoxyuridine (EdU), and Transwell assay. In our study, GNG7 was down-regulated in LUAD, which significantly correlated with survival of LUAD patients. Functional experiments revealed that GNG7 significantly inhibited LUAD cell proliferation, migration, and invasion in vitro and E2F1 overexpression reversed these properties. GNG7 suppressed xenograft tumorigenesis in nude mice models in vivo. In conclusion, GNG7 functions as a tumor suppressor in LUAD cells through inhibiting E2F1.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.082DOI Listing
July 2021

Circular RNA hsa-circ-000881 suppresses the progression of lung adenocarcinoma via a miR-665/PRICKLE2 axis.

Ann Transl Med 2021 Mar;9(6):498

Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Circular RNA (circRNA) has become a new focus in the field of tumor biology research in recent years. Many circRNAs have been showed to play an important role in the progression of lung adenocarcinoma (LUAD). In this work, we studied the oncological role of hsa-circ-000881 in LUAD and attempted to explore the related mechanism.

Methods: The relative expressions of hsa-circ-000881, miR-665, and PRICKLE2 were detected by RT-qPCR or western blot. Functional assays were conducted to analyze the role of hsa-circ-000881 in the proliferation, migration, and invasion of LUAD cells. A luciferase reporter assay was performed to verify whether hsa-circ-000881, miR-665, and PRICKLE2 interact with each other.

Results: Circ-000881 was remarkably downregulated in LUAD. Overexpression of circ-000881 attenuated cell growth, migration, and invasion, whereas its knockdown enhanced the malignancy of LUAD cells. The results of luciferase reporter assay and bioinformatics analysis confirmed that circ-000881 served as a sponge for miR-665, and PRICKLE2 was a direct target of miR-665.Overexpression of miR-665 or silencing of PRICKLE2 abolished circ-000881-mediated inhibition of malignant tumor behavior in LUAD cells.

Conclusions: Circ-000881 has inhibitory effects on LUAD via a miR-665/PRICKLE2 axis, suggesting that circ-000881 may be an underlying therapeutic target for LUAD.
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http://dx.doi.org/10.21037/atm-21-844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039684PMC
March 2021

18β-Glycyrrhetinic acid alleviates demyelination by modulating the microglial M1/M2 phenotype in a mouse model of cuprizone-induced demyelination.

Neurosci Lett 2021 06 1;755:135871. Epub 2021 Apr 1.

Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan University, Wuhan, Hubei, PR China. Electronic address:

This research aimed to examine the nutritious supplementary function of 18β-Glycyrrhetinic acid (18β-GA) in moderating the myelin sheath destruction and behavioral impairments observed in the cuprizone model of demyelination. Mice were fed daily on food containing cuprizone (0.3 %) and given doses of 18β-GA (5 or 1 mg/kg) for a period of five weeks. The groups treated with 18β-GA exhibited improvements in exploratory behavior, locomotive activity, and weight. As assessed using luxol-fast blue and myelin basic protein (MBP) staining, which were used to detect demyelination in the brain, 18β-GA both reduced and prevented instances of cuprizone-induced demyelinating lesions; treatment with 18β-GA also caused the MBP level in the corpus callosum to increase. Furthermore, alongside these positive results following 18β-GA treatment, microglial polarisation was also observed to shift towards the beneficial M2 phenotype. The results of this research thus indicate the potential clinical application of 18β-GA for the prevention of myelin damage and behavioral dysfunction.
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http://dx.doi.org/10.1016/j.neulet.2021.135871DOI Listing
June 2021
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